It is known that a single oncogene, either viral or activated cellular, can cause transformation of mammalian cells in vitro and initiate tumors in animals. The objective of this research is to study the role of such initiating oncogenes in the neoplastic progression that takes place as a tumor develops and changes in the selective environment of the afflicted host, and to ask whether additional oncogenes may be activated during this process. We will transfect NIH3T3 cells with proviral DNA from two different avian sarcoma viruses, which have distinctly different oncogenes. Each will have a ts mutation in its oncogene. The transformed cells will be used to produce tumors in animals, and the tumors will be selected during animal passage for particular alterations in their oncogenic potential. We will then study the state of the avian oncogene as it exists in the cells of the tumors with altered characteristics. We will also determine whether additional oncogenes, derived from their cellular precursors (proto-oncogenes), have been activated. In other words, we are looking for genetic changes that might account for the alterations in the oncogenic potential of the tumor cells as they undergo a selection in the host.